Bottom Line:
Xeroderma pigmentosum (XP) is a rare recessive disorder that is characterized by extreme sensitivity to UV light.The main clinical feature of XP is various forms of skin cancers; however, neurological degeneration is present in XPA, XPB, XPD and XPG complementation groups.Therefore, this analysis has revealed distinct gene expression profiles for the XP complementation groups and the first step towards understanding the neurological symptoms of XP.

ABSTRACTXeroderma pigmentosum (XP) is a rare recessive disorder that is characterized by extreme sensitivity to UV light. UV light exposure results in the formation of DNA damage such as cyclobutane dimers and (6-4) photoproducts. Nucleotide excision repair (NER) orchestrates the removal of cyclobutane dimers and (6-4) photoproducts as well as some forms of bulky chemical DNA adducts. The disease XP is comprised of 7 complementation groups (XP-A to XP-G), which represent functional deficiencies in seven different genes, all of which are believed to be involved in NER. The main clinical feature of XP is various forms of skin cancers; however, neurological degeneration is present in XPA, XPB, XPD and XPG complementation groups. The relationship between NER and other types of DNA repair processes is now becoming evident but the exact relationships between the different complementation groups remains to be precisely determined.Using gene expression analysis we have identified similarities and differences after UV light exposure between the complementation groups XP-A, XP-C, XP-D, XP-E, XP-F, XP-G and an unaffected control. The results reveal that there is a graded change in gene expression patterns between the mildest, most similar to the control response (XP-E) and the severest form (XP-A) of the disease, with the exception of XP-D. Distinct differences between the complementation groups with neurological symptoms (XP-A, XP-D and XP-G) and without (XP-C, XP-E and XP-F) were also identified. Therefore, this analysis has revealed distinct gene expression profiles for the XP complementation groups and the first step towards understanding the neurological symptoms of XP.

Figure 2: Number of genes altered greater than 1.5 fold in control and XP complementation group fibroblasts after 2 J/min UV light treatment. Control and XP fibroblasts cell line cultures were exposed to UV light. Numbers of differentially expressed genes were determined by identifying genes with a greater than 1.5 fold change in expression after UV light exposure. Similar numbers of genes were differentially expressed in the control and XP complementation groups with the exception of XPD which had a considerably higher number of genes down-regulated by greater than 1.5 fold and XPA which had a low number of differentially expressed genes, reflective of the low number of genes expressed in the XPA fibroblasts after UV light exposure percentage of NER activity present in each cell line. XPE has approximately 45% normal NER activity and was the most similar to the control profile as measured by distance on the dendrogram (i.e. there is vertical distance between all the other XP profiles and the branch joining control

Mentions:
The control fibroblasts expressed more genes than any of the XP fibroblast cell lines after UV light irradiation (Fig. 1), indicating that altered expression due to NER deficiency was being detected. Gene expression alterations greater than 1.5 fold, specific to each XP complementation group, were also identified (Fig. 2). Although there was greater expression in the control fibroblasts after UV light treatment, the number of genes altered by greater than 1.5 fold was greater in some XP complementation groups, in particular XPD. Conversely, the XPA fibroblasts showed a low number of genes differentially expressed by greater than 1.5 fold (Fig. 2), which is reflective of the low number of genes expressed by the XPA fibroblast cultures after UV light exposure (Fig. 1).

Figure 2: Number of genes altered greater than 1.5 fold in control and XP complementation group fibroblasts after 2 J/min UV light treatment. Control and XP fibroblasts cell line cultures were exposed to UV light. Numbers of differentially expressed genes were determined by identifying genes with a greater than 1.5 fold change in expression after UV light exposure. Similar numbers of genes were differentially expressed in the control and XP complementation groups with the exception of XPD which had a considerably higher number of genes down-regulated by greater than 1.5 fold and XPA which had a low number of differentially expressed genes, reflective of the low number of genes expressed in the XPA fibroblasts after UV light exposure percentage of NER activity present in each cell line. XPE has approximately 45% normal NER activity and was the most similar to the control profile as measured by distance on the dendrogram (i.e. there is vertical distance between all the other XP profiles and the branch joining control

Mentions:
The control fibroblasts expressed more genes than any of the XP fibroblast cell lines after UV light irradiation (Fig. 1), indicating that altered expression due to NER deficiency was being detected. Gene expression alterations greater than 1.5 fold, specific to each XP complementation group, were also identified (Fig. 2). Although there was greater expression in the control fibroblasts after UV light treatment, the number of genes altered by greater than 1.5 fold was greater in some XP complementation groups, in particular XPD. Conversely, the XPA fibroblasts showed a low number of genes differentially expressed by greater than 1.5 fold (Fig. 2), which is reflective of the low number of genes expressed by the XPA fibroblast cultures after UV light exposure (Fig. 1).

Bottom Line:
Xeroderma pigmentosum (XP) is a rare recessive disorder that is characterized by extreme sensitivity to UV light.The main clinical feature of XP is various forms of skin cancers; however, neurological degeneration is present in XPA, XPB, XPD and XPG complementation groups.Therefore, this analysis has revealed distinct gene expression profiles for the XP complementation groups and the first step towards understanding the neurological symptoms of XP.

ABSTRACTXeroderma pigmentosum (XP) is a rare recessive disorder that is characterized by extreme sensitivity to UV light. UV light exposure results in the formation of DNA damage such as cyclobutane dimers and (6-4) photoproducts. Nucleotide excision repair (NER) orchestrates the removal of cyclobutane dimers and (6-4) photoproducts as well as some forms of bulky chemical DNA adducts. The disease XP is comprised of 7 complementation groups (XP-A to XP-G), which represent functional deficiencies in seven different genes, all of which are believed to be involved in NER. The main clinical feature of XP is various forms of skin cancers; however, neurological degeneration is present in XPA, XPB, XPD and XPG complementation groups. The relationship between NER and other types of DNA repair processes is now becoming evident but the exact relationships between the different complementation groups remains to be precisely determined.Using gene expression analysis we have identified similarities and differences after UV light exposure between the complementation groups XP-A, XP-C, XP-D, XP-E, XP-F, XP-G and an unaffected control. The results reveal that there is a graded change in gene expression patterns between the mildest, most similar to the control response (XP-E) and the severest form (XP-A) of the disease, with the exception of XP-D. Distinct differences between the complementation groups with neurological symptoms (XP-A, XP-D and XP-G) and without (XP-C, XP-E and XP-F) were also identified. Therefore, this analysis has revealed distinct gene expression profiles for the XP complementation groups and the first step towards understanding the neurological symptoms of XP.